Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy.
Int J Mol Sci. 2023 Jan 19;24(3):1969. doi: 10.3390/ijms24031969.
Mitochondrial diseases (MDs) are inherited genetic conditions characterized by pathogenic mutations in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA). Current therapies are still far from being fully effective and from covering the broad spectrum of mutations in mtDNA. For example, unlike heteroplasmic conditions, MDs caused by homoplasmic mtDNA mutations do not yet benefit from advances in molecular approaches. An attractive method of providing dysfunctional cells and/or tissues with healthy mitochondria is mitochondrial transplantation. In this review, we discuss what is known about intercellular transfer of mitochondria and the methods used to transfer mitochondria both in vitro and in vivo, and we provide an outlook on future therapeutic applications. Overall, the transfer of healthy mitochondria containing wild-type mtDNA copies could induce a heteroplasmic shift even when homoplasmic mtDNA variants are present, with the aim of attenuating or preventing the progression of pathological clinical phenotypes. In summary, mitochondrial transplantation is a challenging but potentially ground-breaking option for the treatment of various mitochondrial pathologies, although several questions remain to be addressed before its application in mitochondrial medicine.
线粒体疾病（MDs）是由核 DNA（nDNA）或线粒体 DNA（mtDNA）中的致病性突变引起的遗传性疾病。目前的治疗方法仍远未完全有效，也无法涵盖 mtDNA 中广泛的突变。例如，与异质体情况不同，由同质体 mtDNA 突变引起的 MD 尚未受益于分子方法的进步。为功能失调的细胞和/或组织提供健康线粒体的一种有吸引力的方法是线粒体移植。在这篇综述中，我们讨论了已知的细胞间线粒体转移以及用于在体外和体内转移线粒体的方法，并对未来的治疗应用进行了展望。总的来说，即使存在同质体 mtDNA 变体，含有野生型 mtDNA 拷贝的健康线粒体的转移也可以诱导异质体转移，从而减轻或预防病理性临床表型的进展。总之，线粒体移植是治疗各种线粒体疾病的一项具有挑战性但具有潜在突破性的选择，尽管在将其应用于线粒体医学之前，仍有几个问题需要解决。
